Final Recommendation Statement
Cardiovascular Disease: Risk Assessment With Nontraditional Risk Factors
July 10, 2018
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
The US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific clinical preventive services for patients without obvious related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
Cardiovascular disease is the most common cause of death among adults in the United States. Treatment to prevent CVD events by modifying risk factors is currently informed by the Framingham Risk Score, the Pooled Cohort Equations, or similar CVD risk assessment models. If current CVD risk assessment models could be improved by adding more risk factors, treatment might be better targeted, thereby maximizing the benefits and minimizing the harms.
The USPSTF found adequate evidence that adding the ABI, hsCRP level, or CAC score to existing CVD risk assessment models (Framingham Risk Score [which estimates a person’s 10-year risk of coronary heart disease] or Pooled Cohort Equations [which estimate 10-year risk of myocardial infarction, death from coronary heart disease, or stroke]) may improve calibration (agreement between observed and predicted outcomes), discrimination (ability to distinguish between people who will and will not experience an event), and reclassification (ability to correctly reassign people into clinically meaningful risk strata ). The USPSTF chose to review these 3 nontraditional risk factors because prior evidence reviews identified them as the most promising to improve on existing CVD risk assessment tools.
Benefits of Risk Assessment and Intervention
The USPSTF found inadequate evidence to assess whether treatment decisions guided by ABI, hsCRP level, or CAC score test results, when added to existing CVD risk assessment models, lead to reduced incidence of CVD events or mortality.
Harms of Risk Assessment and Intervention
The USPSTF found adequate evidence to bound the harms of risk assessment and intervention as small. When direct evidence is limited, absent, or restricted to select populations or clinical scenarios, the USPSTF may place conceptual upper or lower bounds on the magnitude of benefit or harms. Harms can include abnormal test results, inappropriate risk reclassification, and incidental findings leading to additional testing and possible procedures, as well as anxiety.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adding the ABI, hsCRP level, or CAC score to traditional risk assessment for CVD in asymptomatic adults to prevent CVD events.
This recommendation applies to asymptomatic adults without a history of CVD.
Suggestions for Practice Regarding the I Statement
Although in the United States both the Framingham Risk Score and the Pooled Cohort Equations are used in practice, the USPSTF recommends that clinicians use the Pooled Cohort Equations to assess CVD risk and to guide treatment decisions until further evidence shows additional benefit of adding other CVD risk factors.
Potential Preventable Burden
Cardiovascular disease comprises diseases of the heart and vascular system, including atherosclerosis, cerebrovascular disease, and peripheral artery disease. It is the most common cause of death among adults in the United States, accounting for 1 in 3 deaths each year.1 Although CVD remains a significant cause of morbidity and mortality, CVD mortality has been decreasing over time in the United States. Currently, the annual incidence of new cases of myocardial infarction and cerebrovascular accident in the United States is 580,000 and 610,000, respectively.1
The incidence of CVD varies by sex. Men, on average, develop CVD about 10 years earlier than women.2 The burden of CVD increases with age. In 2015, the age-adjusted prevalence of coronary artery disease among US adults aged 45 to 64 years was 6.1%, compared with 16.4% among those aged 65 to 74 years and 23.3% among those 75 years or older.3 In the same year, 2.7%, 5.6%, and 11.2% of US adults in these age groups, respectively, experienced a stroke. Prevalence also varies by race/ethnicity; in 2015, the prevalence of coronary artery disease was 2 times greater among American Indian/Alaskan Native adults than Asian adults (9.3% vs 3.7%, respectively). Prevalence in Hispanic, African American, and white adults was similar, at 5.1%, 5.4%, and 5.6%, respectively.3 However, strokes were most common among African American adults (3.7%), followed by white (2.4%), Hispanic (2.4%), American Indian/Alaska Native (2.2%), and Asian (1.4%) adults.
Testing for hsCRP level and the ABI is noninvasive, and there is little direct harm from the tests. Harms of testing for CAC score include exposure to radiation and incidental findings on computed tomography of the chest, such as pulmonary nodules, that may lead to further invasive testing and procedures. Abnormal test results may lead to further testing, procedures, and lifelong medication use without proof of benefit but with expense and potential adverse effects for the patient. Psychological harms may result from reclassification into a higher-risk category for CVD events.
Only 1 of the risk assessment models currently used in the United States, the Reynolds Risk Score, incorporates hsCRP level into its risk calculation. A number of guidelines, including those from the American College of Cardiology and the American Heart Association, recommend considering hsCRP level, the ABI, or CAC score to clarify treatment decisions for patients whose risk assessment is borderline or unclear using a traditional risk assessment model.
Assessment of Risk
Accurate identification of persons at high risk for CVD events, particularly nonfatal myocardial infarction or stroke, and CVD death provides the opportunity for more intensive risk factor management to reduce the likelihood of such an event. In addition, identifying persons at low risk may allow for a reduction in interventions with a low benefit to risk ratio for those not likely to benefit.
Several traditional risk factors are associated with higher risk for CVD events, including older age, male sex, high blood pressure, current smoking, abnormal cholesterol levels, diabetes, obesity, and physical inactivity. Risk factors can be combined in many ways to classify a person’s risk for a CVD event as low, intermediate, or high. Several calculators and models are available to quantify a person’s 10-year CVD event risk. The Framingham Risk Score (which estimates a person’s 10-year risk of coronary heart disease) was 1 of the first widely used risk assessment tools. Persons with a 10-year CVD event risk greater than 20% are generally considered at high risk, those with a 10-year risk less than 10% are considered at low risk, and those in the 10% to 20% range are considered at intermediate risk. The Pooled Cohort Equations (which estimate 10-year risk of myocardial infarction, death from coronary heart disease, or stroke) were introduced in 2013 and were developed using more contemporary and diverse cohort data, with the inclusion of race/ethnicity and diabetes. Persons with a 10-year CVD event risk less than 7.5% are considered at low risk, and those with a 10-year risk of 7.5% or greater are considered at high risk.4 The distribution of estimated CVD risk in the US population is highly influenced by age and sex. Population estimates of the distribution of 10-year CVD event risk assessed by the Pooled Cohort Equations, which categorize risk using somewhat different thresholds, and using 2001-2010 data from the National Health and Nutrition Examination Survey show that the vast majority of US adults aged 40 to 49 years have an estimated 10-year CVD event risk of 7% or less (93% of women and 81% of men). Among US adults aged 50 to 59 years, 80% of women and 46% of men have an estimated 10-year CVD event risk of 7% or less; 42% of women and 7% of men aged 60 to 69 years have an estimated 10-year CVD event risk of 7% or less.5
Cardiovascular disease risk assessment in the United States has been generally based on the Framingham Risk Score and, more recently, the Pooled Cohort Equations. However, both have been documented to overestimate and underestimate risk in some persons. Therefore, identification of additional tests (for nontraditional risk factors) that could improve risk prediction, including the ABI, hsCRP level, and CAC score, is of interest.
The ABI is the ratio of the systolic blood pressure at the ankle (measuring the pressure proximal to the dorsalis pedis or posterior tibial artery) to the systolic blood pressure at the brachial artery. A value less than 0.9 indicates peripheral artery disease.6
High-sensitivity C-reactive protein is a serum protein involved in inflammatory and immune responses. Testing for hsCRP level involves a single blood sample, and the test is widely available. A threshold of greater than 2 or 3 mg/L is used in clinical practice to signify increased cardiovascular risk.7-9
Coronary artery calcium score is obtained by electron-beam or multidetector computed tomography, which measure the calcium content in the coronary arteries. Scoring systems and thresholds for an elevated CAC score vary across studies, but the baseline comparison is often a CAC score of 0.10
Treatment and Interventions
Asymptomatic adults at increased risk for CVD are usually treated with a combination of diet and exercise modifications, statins, aspirin, blood pressure management, and smoking cessation interventions.
Additional Approaches to Prevention
The National Heart, Lung, and Blood Institute provides resources on cardiovascular risk assessment, including a link to an online version of the Pooled Cohort Equations.11 Healthy People 2020 provides a database of evidence-based resources for achieving Healthy People 2020 goals, including interventions to prevent CVD.12
The USPSTF has made recommendations on many factors related to CVD prevention, including screening for high blood pressure,13 statin use,14 counseling on smoking cessation,15 counseling on healthful diet and physical activity,16 and screening for peripheral artery disease and CVD risk assessment with the ABI.17 In addition, the USPSTF recommends low-dose aspirin use in certain persons at increased risk for CVD.18
Research Needs and Gaps
A substantial number of studies demonstrate an association between the ABI, hsCRP level, and CAC score and cardiovascular outcomes, so additional association studies are unlikely to add more information. Similarly, studies assessing nontraditional risk factors in isolation are of limited value, given that current treatment recommendations are based on risk assessment with the Framingham Risk Score or Pooled Cohort Equations. Good-quality studies comparing traditional risk assessment with traditional risk assessment plus the ABI, hsCRP level, or CAC scores are needed to measure the effect of adding nontraditional risk factors on clinical decision thresholds and patient outcomes (CVD events and mortality). Studies are especially needed in more diverse populations (women, racial/ethnic minorities, persons of lower socioeconomic status), in whom assessment of nontraditional risk factors may help address the shortcomings of traditional risk models. In addition, well-designed prospective studies reflective of real-world practice are needed to identify the downstream effects of CAC score on additional testing and procedures.
Burden of Disease
Cardiovascular disease is the most common cause of death among adults in the United States, accounting for 1 in 3 deaths each year. Although it remains a major cause of morbidity and mortality, CVD mortality has been decreasing over time in the United States. Currently, the annual incidence of new cases of myocardial infarction and cerebrovascular accident in the United States is 580,000 and 610,000, respectively.1
Scope of Review
The USPSTF commissioned a systematic evidence review7,19 to update its 2009 recommendation on using nontraditional risk factors in assessment of coronary heart disease risk.20 Unlike the 2009 recommendation, the current recommendation focuses on 3 nontraditional risk factors—the ABI, hsCRP level, and CAC score. The USPSTF chose these risk factors because they have the most promising evidence base, are reliably measured, are independently associated with CVD risk or CVD events, and the prevalence and distribution of abnormal and normal values have been described in the target population. The review focused on the health benefits (reduction in CVD events, CVD mortality, and overall mortality) and harms of CVD risk assessment and treatment guided by nontraditional risk factors combined with the Pooled Cohort Equations or Framingham Risk Score compared with using either risk assessment model alone. The review also evaluated whether the use of nontraditional risk factors, when added to existing CVD risk assessment models, improves measures of calibration, discrimination, and risk reclassification.
At the same time, the USPSTF also commissioned a separate systematic evidence review to update its 2013 recommendation on screening for peripheral artery disease and CVD risk assessment with the ABI.21
Accuracy of Screening Tests
The USPSTF reviewed evidence of whether the ABI, hsCRP level, or CAC score improves calibration, discrimination, or risk reclassification when added to CVD risk assessment models using traditional risk factors. Calibration measures the agreement between observed and predicted outcomes, discrimination measures the ability to distinguish between persons who will and will not have an event, and reclassification measures the ability to (correctly) reassign persons into clinically meaningful risk strata. The USPSTF found 10 articles representing 22 cohorts for the ABI, 25 articles representing 49 cohorts for hsCRP level, and 19 articles representing 10 cohorts for CAC score, although few studies reported all 3 measures; most did not use the published versions of the Framingham Risk Score or the Pooled Cohort Equations as the base model.
In general, all cohort studies examining calibration (5 for the ABI, 9 for hsCRP level, and 8 for CAC score) found that adding 1 of these 3 nontraditional risk factors improved calibration, although preferred measures of calibration were rarely reported and only 1 study (of CAC score) used the Pooled Cohort Equations as a base model. The calibration plots available for hsCRP demonstrate that, although adding hsCRP level improved calibration for some groups, it worsened calibration for others.22,23 An individual patient data meta-analysis of 18 cohorts found that the ABI improved discrimination when added to the Framingham Risk Score, but only for women.24 A separate analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (which was not included in the individual patient data meta-analysis) found no improvement from adding the ABI to the Pooled Cohort Equations.25 Evidence (25 studies) for adding hsCRP was inconsistent, showing at most a small improvement in discrimination.7 In the only study that added hsCRP to the Pooled Cohort Equations (MESA), hsCRP level did not improve discrimination.25 Adding CAC score (18 studies) to various risk assessment models resulted in at least a small, and often larger, improvement in discrimination.7 However, the magnitude of improvement decreased as the discrimination of the base model improved. Four studies25-28 that added CAC score to the Pooled Cohort Equations found a very small to small improvement (0.02-0.04) to the area under the curve.
The evidence for risk reclassification was largely similar to the evidence for discrimination. Different studies used different risk strata, but those that used the Framingham Risk Score as the base model generally used less than 10% for low risk, 10% to 20% for intermediate risk, and greater than 20% for high risk, while studies using the Pooled Cohort Equations as the base model used greater than 7.5% for increased risk. In general, studies found that the ABI, hsCRP level, and CAC score tended to have positive event net reclassification (ie, more persons who had a CVD event were correctly reclassified to a higher-risk category than were incorrectly reclassified to a lower-risk category). The ABI (in women) and CAC score tended to have negative nonevent net reclassification (ie, more persons who did not have a CVD event were incorrectly reclassified to a higher-risk category than were correctly reclassified to a lower-risk category). Because only a few persons in the general population have CVD events (myocardial infarction, stroke, or CVD death) in a given period, this suggests that on balance, more persons would be inappropriately than appropriately reclassified.7
Effectiveness of Risk Assessment and Treatment
The USPSTF found only 1 study that directly assessed the potential benefit on clinical outcomes of adding 1 of these 3 nontraditional risk factors to traditional risk assessment models.29 This fair-quality randomized clinical trial (RCT) assigned asymptomatic volunteers (N = 2137) with no history of CVD to CAC scoring plus risk factor assessment counseling vs risk factor assessment counseling alone. At 4 years, there was no difference in CVD outcomes between the 2 groups; however, the study was not adequately powered to detect a difference in patient health outcomes.29 The USPSTF found no studies that assessed the incremental benefit on health outcomes of adding the ABI or hsCRP level to traditional risk factor assessment. The Viborg Vascular (VIVA) screening trial30 recently reported interim results; this trial randomized men aged 65 to 74 years to invitation for a triple screening (screening for high blood pressure, abdominal aortic aneurysm, and peripheral artery disease using the ABI) or no screening and found a decrease in mortality with screening; however, it was not possible to determine how much of the decrease was attributable to screening for peripheral artery disease and how much was attributable to screening for abdominal aortic aneurysm and high blood pressure, both of which are already recommended screenings.
The USPSTF found no trials evaluating the additional benefit of adding the ABI, hsCRP level, or CAC score to traditional risk assessment models for guiding decisions about specific interventions to prevent CVD. The USPSTF found a few studies evaluating the use of a nontraditional risk factor as a single intervention to guide decisions about specific preventive medications compared with usual care. Two RCTs (total N = 4626) compared using the ABI to guide decisions to start aspirin therapy vs usual care and found no benefit in CVD outcomes at 7 years of follow-up.31,32 However, both studies used atypical cutoff points for diagnosing peripheral artery disease, and the results may not be applicable to current practice. One RCT (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin [JUPITER]; N = 17,802) compared hsCRP screening vs usual care to guide high-intensity statin therapy and found benefit at 1.9 years of follow-up in the reduction of CVD events in the hsCRP group.9 However, because the study only randomized persons with elevated hsCRP levels, it is not known whether patients with lower hsCRP levels would also have benefited from high-intensity statin therapy. Further, many of these patients met criteria for statin therapy based on traditional CVD risk assessment and would already have been candidates for treatment. One study (n = 1005) of using CAC score to guide statin therapy found no benefit at 4 years in the reduction of CVD events.33
A systematic review that addressed the effect of screening with CAC score on risk perception, adherence to medication, and behavioral therapies found only 2 studies comparing traditional CVD risk assessment vs CAC score. Neither of these studies found that screening with CAC score was superior to traditional CVD risk assessment for preventive medication use or risk factor management.5
Potential Harms of Screening and Treatment
The main potential harm of adding nontraditional risk factors to CVD risk assessment is radiation exposure from CAC score testing, although the dosage (0.4 to 2.1 mSv) is relatively low.7 More general potential harms are false-positive test results and subsequent invasive diagnostic procedures (such as coronary angiography). Three studies assessing the effect of CAC score on health care utilization found conflicting results. The Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research (EISNER) study, an RCT of CAC score use in an academic setting, found no statistically significant increase in downstream cardiac testing and procedures.29 In contrast, a retrospective study of Medicare data found that use of CAC score increased downstream cardiac testing and procedures compared with use of hsCRP and lipid screening,34 while a second smaller observational study found no difference.35 A systematic review of 7 studies found that the prevalence of incidental findings on computed tomography for CAC score ranged from 8% to 58%. The ultimate outcomes of subsequent diagnostic procedures for these incidental findings, whether positive or negative, are not known.36 Two studies found no short-term psychological harms from use of CAC score in CVD risk assessment.37,38
Treatment with aspirin and statins to prevent CVD events has some potential harms (specifically bleeding and increased incidence of diabetes, respectively), but these harms are generally accepted to be a reasonable trade-off among persons at higher risk of CVD events.39
Estimate of Magnitude of Net Benefit
The USPSTF found adequate evidence that adding the ABI, hsCRP level, and CAC score to existing CVD risk assessment models results in small improvements in discrimination and reclassification. However, the clinical meaning of these changes is largely unknown. Evidence on adding the ABI, hsCRP level, and CAC score to the Pooled Cohort Equations is sparse, which makes it difficult to infer the clinical significance of these findings. The USPSTF found inadequate evidence to assess whether treatment decisions guided by the ABI, hsCRP level, or CAC score, in addition to risk factors in existing CVD risk assessment models, leads to reduced incidence of CVD events or mortality. Few studies were available and were either underpowered or used atypical test thresholds for intervention. The USPSTF found adequate evidence to bound the harms of early detection and interventions as small. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using the ABI, hsCRP level, or CAC score in risk assessment for CVD in asymptomatic adults to prevent CVD events.
Response to Public Comment
A draft version of this recommendation statement was posted for public comment on the USPSTF website from January 16, 2018, to February 12, 2018. Many comments expressed belief that the evidence for risk assessment with CAC score was strong enough to warrant a separate positive recommendation. Although adding CAC score to traditional risk assessment models improved discrimination and reclassification, the USPSTF found inadequate evidence that this change would translate into improved health outcomes among asymptomatic patients.
Several comments expressed concern that the USPSTF overestimated the harms associated with CAC score testing (radiation exposure, downstream testing). The USPSTF added language to clarify that it determined that the harms associated with the addition of nontraditional risk factors, including CAC score, are small in magnitude.
Several comments noted that the addition of nontraditional risk factors, especially CAC score, is useful for patients whose risk stratification is unclear or for those who fall into intermediate-risk groups. The USPSTF did not find convincing evidence that adding nontraditional risk factors to traditional risk factors improves reclassification in intermediate-risk groups. As clinical practice moves toward a single threshold for treatment, this concern may no longer be relevant in clinical decision making. Some comments also expressed belief that CAC score testing leads to better adherence to preventive therapies (ie, medications and lifestyle changes). The USPSTF carefully reviewed the available evidence and concluded that CAC score testing showed no benefit over traditional CVD risk assessment in preventive medication use or risk factor control. The USPSTF added language to address this point.
Several comments recommended including more information on the differences between the Framingham Risk Score and the Pooled Cohort Equations as well as population distribution of risk. The USPSTF included information in the Clinical Considerations section to clarify these differences and provide more information on risk in the general US population. Last, comments noted that the USPSTF assessment may not be applicable across sex, race/ethnicity, family history, and socioeconomic status. The USPSTF included language indicating the need for more studies in these subpopulations.
This recommendation replaces the 2009 USPSTF recommendation.20 The previous recommendation considered the evidence on the addition of several risk factors to the Framingham Risk Score. The major change in the current recommendation is that the USPSTF evaluated the Pooled Cohort Equations in addition to the Framingham Risk Score and focused on only 3 nontraditional risk factors—the ABI, hsCRP level, and CAC score.
The American Association of Clinical Endocrinologists’ 2017 guidelines include hsCRP level, as part of the Reynolds Risk Score, as a possible CVD risk assessment tool and to stratify borderline cases, and also states that CAC score can be useful in refining risk stratification.40 The American College of Cardiology and American Heart Association encourage using the Pooled Cohort Equations to assess 10-year risk of an initial hard CVD event (defined as stroke, nonfatal myocardial infarction, or CVD death). If risk-based treatment is still uncertain, they recommend using 1 or more of the nontraditional risk factors (including the ABI, hsCRP level, or CAC score) or family history to help clarify treatment decisions.4 The Canadian Cardiovascular Society encourages use of a modified Framingham Risk Score risk assessment tool in asymptomatic persons to assess 10-year risk of any CVD event. It recommends judicious use of secondary testing among patients for whom the need for statin therapy is unclear.41 The European Society of Cardiology uses the Systemic Coronary Risk Evaluation (SCORE) risk charts, which do not include the ABI, hsCRP level, or CAC score, to determine 10-year risk of a fatal CVD event.42 The UK National Institute for Health and Care Excellence uses the QRISK3 risk tool, which does not include the ABI, hsCRP level, or CAC score, to estimate 10-year risk of a CVD event.43 The Scottish Intercollegiate Guidelines Network (SIGN) uses the ASSIGN risk score to determine the 10-year risk of a CVD event, which does not include the ABI, hsCRP level, or CAC score.44
The US Preventive Services Task Force (USPSTF) members include the following individuals: Susan J. Curry, PhD (University of Iowa, Iowa City); Alex H. Krist, MD, MPH (Fairfax Family Practice Residency, Fairfax, Virginia, and Virginia Commonwealth University, Richmond); Douglas K. Owens, MD, MS (Veterans Affairs Palo Alto Health Care System, Palo Alto, California, and Stanford University, Stanford, California); Michael J. Barry, MD (Harvard Medical School, Boston, Massachusetts); Aaron B. Caughey, MD, PhD (Oregon Health & Science University, Portland); Karina W. Davidson, PhD, MASc (Columbia University, New York, New York); Chyke A. Doubeni, MD, MPH (University of Pennsylvania, Philadelphia); John W. Epling Jr, MD, MSEd (Virginia Tech Carilion School of Medicine, Roanoke); Alex R. Kemper, MD, MPH, MS (Nationwide Children’s Hospital, Columbus, Ohio); Martha Kubik, PhD, RN (Temple University, Philadelphia, Pennsylvania); Seth Landefeld, MD (University of Alabama at Birmingham); Carol M. Mangione, MD, MSPH (University of California, Los Angeles); Michael Silverstein, MD, MPH (Boston University, Boston, Massachusetts); Melissa A. Simon, MD, MPH (Northwestern University, Evanston, Illinois); Chien-Wen Tseng, MD, MPH, MSEE (University of Hawaii, Honolulu, and Pacific Health Research and Education Institute, Honolulu, Hawaii); John B. Wong, MD (Tufts University School of Medicine, Boston, Massachusetts).
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Authors followed the policy regarding conflicts of interest described at https://www.uspreventiveservicestaskforce.org/Page/Name/conflict-of-interest-disclosures. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. No other disclosures were reported.
Funding/Support: The USPSTF is an independent, voluntary body. The US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF.
Disclaimer: Recommendations made by the USPSTF are independent of the US government. They should not be construed as an official position of AHRQ or the US Department of Health and Human Services.
Copyright Notice: USPSTF recommendations are based on a rigorous review of existing peer-reviewed evidence and are intended to help primary care clinicians and patients decide together whether a preventive service is right for a patient's needs. To encourage widespread discussion, consideration, adoption, and implementation of USPSTF recommendations, AHRQ permits members of the public to reproduce, redistribute, publicly display, and incorporate USPSTF work into other materials provided that it is reproduced without any changes to the work of portions thereof, except as permitted as fair use under the US Copyright Act.
AHRQ and the US Department of Health and Human Services cannot endorse, or appear to endorse, derivative or excerpted materials, and they cannot be held liable for the content or use of adapted products that are incorporated on other Web sites. Any adaptations of these electronic documents and resources must include a disclaimer to this effect. Advertising or implied endorsement for any commercial products or services is strictly prohibited.
This work may not be reproduced, reprinted, or redistributed for a fee, nor may the work be sold for profit or incorporated into a profit-making venture without the express written permission of AHRQ. This work is subject to the restrictions of Section 1140 of the Social Security Act, 42 U.S.C. §320b-10. When parts of a recommendation statement are used or quoted, the USPSTF Web page should be cited as the source.
1. Benjamin EJ, Blaha MJ, Chiuve SE, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146-e603.
2. Mozaffarian D, Benjamin EJ, Go AS, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation . 2015;131(4):e29-e322.
3. Centers for Disease Control and Prevention (CDC). Summary Health Statistics: National Health Interview Survey, 2015. Table A-1a: Age-adjusted percentages (with standard errors) of selected circulatory diseases among adults aged 18 and over, by selected characteristics: United States, 2015. CDC website. https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2015_SHS_Table_A-1.pdf. Accessed May 22, 2018.
4. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2014;63(25, pt B):2935-2959.
5. Mamudu HM, Paul TK, Veeranki SP, Budoff M. The effects of coronary artery calcium screening on behavioral modification, risk perception, and medication adherence among asymptomatic adults: a systematic review. J Atherosclerosis . 2014;236(2):338-350.
6. Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med . 2001;344(21):1608-1621.
7. Lin JS, Evans CV, Johnson E, et al. Nontraditional Risk Factors in Cardiovascular Disease Risk Assessment: An Evidence Update for the U.S. Preventive Services Task Force: Evidence Synthesis No. 166. Rockville, MD: Agency for Healthcare Research and Quality; 2018. AHRQ publication 17-05225-EF-1.
8. Buckley DI, Fu R, Freeman M, Rogers K, Helfand M. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med . 2009;151(7):483-495.
9. Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med . 2008;359(21):2195-2207.
10. Helfand M, Buckley DI, Freeman M, et al. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med . 2009;151(7):496-507.
11. National Heart, Lung, and Blood Institute (NHLBI). Assessing cardiovascular risk: systematic evidence review from the risk assessment work group. NHLBI website. https://www.nhlbi.nih.gov/health-topics/assessing-cardiovascular-risk. 2013. Accessed May 22, 2018.
12. Healthy People 2020. Evidence-based resources. HealthyPeople.gov website. https://www.healthypeople.gov/2020/tools-resources/Evidence-Based-Resources. 2018. Accessed May 22, 2018.
13. U.S. Preventive Services Task Force. Screening for high blood pressure in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2015;163(10):778-786.
14. US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA . 2016;316(19):1997-2007.
15. U.S. Preventive Services Task Force. Behavioral and pharmacotherapy interventions for tobacco smoking cessation in adults, including pregnant women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2015;163(8):622-634.
16. U.S. Preventive Services Task Force. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults with cardiovascular risk factors: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2014;161(8):587-593.
17. US Preventive Services Task Force. Screening for peripheral artery disease and cardiovascular disease risk assessment with the ankle-brachial index: US Preventive Services Task Force recommendation statement [published July 10, 2018]. JAMA . doi:10.1001/jama.2018.8357
18. U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2016;164(12):836-845.
19. Lin JS, Evans CV, Johnson E, Redmond N, Coppola EL, Smith N. Nontraditional risk factors in cardiovascular disease risk assessment: updated evidence report and systematic review for the US Preventive Services task Force [published online July 10, 2018]. JAMA . doi:10.1001/jama.2018.4242
20. U.S. Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2009;151(7):474-482.
21. U.S. Preventive Services Task Force. Screening for peripheral artery disease and cardiovascular disease risk assessment with the ankle-brachial index in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2013;159(5):342-348.
22. Shah T, Casas JP, Cooper JA, et al. Critical appraisal of CRP measurement for the prediction of coronary heart disease events: new data and systematic review of 31 prospective cohorts. Int J Epidemiol . 2009;38(1):217-231.
23. Cook NR, Buring JE, Ridker PM. The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med . 2006;145(1):21-29.
24. Fowkes FG, Murray GD, Butcher I, et al; Ankle Brachial Index Collaboration. Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events. Eur J Prev Cardiol. 2014;21(3):310-320.
25. Yeboah J, Young R, McClelland RL, et al. Utility of nontraditional risk markers in atherosclerotic cardiovascular disease risk assessment. J Am Coll Cardiol . 2016;67(2):139-147.
26. Bos D, Leening MJ, Kavousi M, et al. Comparison of atherosclerotic calcification in major vessel beds on the risk of all-cause and cause-specific mortality: the Rotterdam study. Circ Cardiovasc Imaging . 2015;8(12):e003843.
27. Kavousi M, Desai CS, Ayers C, et al. Prevalence and prognostic implications of coronary artery calcification in low-risk women: a meta-analysis. JAMA . 2016;316(20):2126-2134.
28. Fudim M, Zalawadiya S, Patel DK, Egolum UO, Afonso L. Data on coronary artery calcium score performance and cardiovascular risk reclassification across gender and ethnicities. Data Brief. 2016;6:578-581.
29. Rozanski A, Gransar H, Shaw LJ, et al. Impact of coronary artery calcium scanning on coronary risk factors and downstream testing: the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial. J Am Coll Cardiol . 2011;57(15):1622-1632.
30. Lindholt JS, Søgaard R. Population screening and intervention for vascular disease in Danish men (VIVA): a randomised controlled trial. Lancet . 2017;390(10109):2256-2265.
31. Fowkes FG, Price JF, Stewart MC, et al; Aspirin for Asymptomatic Atherosclerosis Trialists. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA . 2010;303(9):841-848.
32. Belch J, MacCuish A, Campbell I, et al; Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh. The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ . 2008;337:a1840.
33. Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. J Am Coll Cardiol . 2005;46(1):166-172.
34. Shreibati JB, Baker LC, McConnell MV, Hlatky MA. Outcomes after coronary artery calcium and other cardiovascular biomarker testing among asymptomatic Medicare beneficiaries. Circ Cardiovasc Imaging . 2014;7(4):655-662.
35. Chi WC, Sylwestrzak G, Barron J, Kasravi B, Power T, Redberg R. Does CAC testing alter downstream treatment patterns for cardiovascular disease? Am J Manag Care. 2014;20(8):e330-e339.
36. Jacobs PC, Mali WP, Grobbee DE, van der Graaf Y. Prevalence of incidental findings in computed tomographic screening of the chest: a systematic review. J Comput Assist Tomogr. 2008;32(2):214-221.
37. Nielsen AD, Videbech P, Gerke O, et al. Population screening for coronary artery calcification does not increase mental distress and the use of psychoactive medication. J Thorac Imaging. 2012;27(3):202-206.
38. O’Malley PG, Feuerstein IM, Taylor AJ. Impact of electron beam tomography, with or without case management, on motivation, behavioral change, and cardiovascular risk profile: a randomized controlled trial. JAMA . 2003;289(17):2215-2223.
39. Dehmer SP, Maciosek MV, Flottemesch TJ. Aspirin Use to Prevent Cardiovascular Disease and Cancer: A Decision Analysis. Rockville, MD: Agency for Healthcare Research and Quality; 2015. AHRQ publication 15-05229-EF-1.
40. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23(suppl 2):1-87.
41. Anderson TJ, Grégoire J, Hegele RA, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151-167.
42. Perk J, De Backer G, Gohlke H, et al; European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635-1701.
43. National Institute for Health and Care Excellence (NICE). Cardiovascular disease: risk assessment and reduction, including lipid modification. NICE website. https://www.nice.org.uk/guidance/cg181. Published 2014. Accessed May 22, 2018.
44. Scottish Intercollegiate Guidelines Network (SIGN). SIGN 149: Risk Estimation and the Prevention of Cardiovascular Disease: A National Clinical Guideline. SIGN website. http://www.sign.ac.uk/assets/sign149.pdf. Published 2017. Accessed May 22, 2018.